Pneumococcal surface protein A (PspA) is an immunodominant and protective surface protein antigen of S. pneumoniae. A truncated version of PspA has been cloned and expressed at a high level in a Salmonella vaccine strain, in which genes encoding for adenylate cyclase and CAMP receptor protein have been deleted. Mice immunized through oral route or intranasally with the recombinant Salmonella-PspA vaccine stimulated the humoral and mucosal immune systems inducing high serum titers anti-PspA antibodies of IgG, IgM and IgA types and significant levels of IgA in Mucosal secretions. The recombinant Salmonella-PspA vaccine induced immunoprotective responses in orally vaccinated mice and significant levels of protection were observed against challenge with the virulent pneumococcal type 2, WU2. Bacterial cells of several pneumococcal vaccine types including 1, 9V, 12F, 20, 23F and 33F were tested for cross-reactive antigen by histochemical enzyme and fluorescent antibody staining methods using PspA monoclonal antibody preparations. Positive reactions to all types were observed with monoclonal antibodies to recombinant PspA antigen whereas partial responses to types 1, 9V, 19F and 20 were found in mouse lung washing samples. Mouse vaginal secretions did not show immunologic reactions with these strains.